The retrotrapezoid nucleus (RTN) and the pre-Boetzinger complex/intermediate ventral respiratory group (pre-Boetc/iVRG) near the ventrolateral medullary (VLM) surface are critical for breathing in anesthetized and reduced preparations. However, studies on goats during surface VLM cooling suggest important differences between anesthetized, awake and NREM sleep states in VLM control of breathing and respiratory pump (RP) and upper airway (UAW) muscle activity. Surface cooling cannot, though, identify cell groups nor elucidate their physiologic functions. The objective of this proposal is to study the role of the RTN and pre-Boetc/iVRG in control of breathing and RP/UAW muscles during awake and NREM sleep states. To create reversible neuronal dysfunction in goats, excitatory amino acid receptor antagonists will be injected into the RTN or pre-Boetc/iVRG through guide tubes chronically implanted bilaterally. Hypotheses include: 1) under anesthesia, injections of non-selective receptor antagonists into the RTN or pre-Boetc/iVRG will cause apnea; 2) in awake and NREM sleep states, antagonist injection into the RTN and pre-Boetc will only slightly alter the timing and drive of breathing during eupnea; 3) antagonist injections into both cell groups will attenuate ventilatory responses to carbon dioxide, oxygen and exercise; 4) antagonist injections into the RTN will reduce the activity of UAW muscles more than RP muscles. Validation of these hypotheses would indicate that during awake and NREM sleep states, respiratory rhythm is not critically dependent on the RTN or pre-Boetc, although each site is important in the control of breathing and RP/UAW muscles. The data will enhance understanding of diseases such as brain-stem stroke, congenital central alveolar hypoventilation, and central and obstructive sleep apnea.